EP0347845A3 - Insulin precursors, their preparation, and dna sequences, expression vehicles and primers and a process for producing human insulin and analogues - Google Patents
Insulin precursors, their preparation, and dna sequences, expression vehicles and primers and a process for producing human insulin and analogues Download PDFInfo
- Publication number
- EP0347845A3 EP0347845A3 EP19890111221 EP89111221A EP0347845A3 EP 0347845 A3 EP0347845 A3 EP 0347845A3 EP 19890111221 EP19890111221 EP 19890111221 EP 89111221 A EP89111221 A EP 89111221A EP 0347845 A3 EP0347845 A3 EP 0347845A3
- Authority
- EP
- European Patent Office
- Prior art keywords
- insulin
- amino acid
- precursors
- acid residues
- human insulin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title abstract 11
- 102000004877 Insulin Human genes 0.000 title abstract 5
- 108090001061 Insulin Proteins 0.000 title abstract 5
- 229940125396 insulin Drugs 0.000 title abstract 5
- 239000002243 precursor Substances 0.000 title abstract 5
- 101000976075 Homo sapiens Insulin Proteins 0.000 title abstract 4
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 title abstract 4
- 108091028043 Nucleic acid sequence Proteins 0.000 title abstract 2
- 125000000539 amino acid group Chemical group 0.000 abstract 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 abstract 1
- 239000005864 Sulphur Substances 0.000 abstract 1
- 150000001413 amino acids Chemical group 0.000 abstract 1
- 238000012258 culturing Methods 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 239000001963 growth medium Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Abstract
B(1-29)-X₁-X₂-Y₂-Y₁-A(1-21)
wherein B(1-29) are the 29 first amino acid residues of the B chain of human insulin, A(1-21) are the 21 amino acid residues of the A chain of human insulin, X₁ represents a peptide bond or one or more amino acid residues, X₂ represents Glu or Asp, and Y₁ and Y₂ each represent Lys or Arg, the positions A6 and A11, A7 and B7 and A20 and B19, respectively, being connected through sulphur bridges, and, optionally, one or more of the amino acid residues of chains B(1-29) and A(1-21) are substituted by another amino acid residue. The insulin precursors are prepared by culturing a yeast strain transformed with a replicable expression vehicle comprising a DNA sequence encoding the insulin precursor and isolating it from the culture medium. The insulin precursors can be converted into human insulin or insulin analogues by enzymatic treatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT89111221T ATE93239T1 (en) | 1988-06-20 | 1989-06-20 | INSULIN PRECURSORS, THEIR PRODUCTION AND DNA SEQUENCES, EXPRESSION VEHICLES AND PRIMERS AND A PROCESS FOR THE PRODUCTION OF HUMAN INSULIN AND ANALOGUES. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK336188A DK336188D0 (en) | 1988-06-20 | 1988-06-20 | propeptides |
| DK3361/88 | 1988-06-20 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0347845A2 EP0347845A2 (en) | 1989-12-27 |
| EP0347845A3 true EP0347845A3 (en) | 1991-07-03 |
| EP0347845B1 EP0347845B1 (en) | 1993-08-18 |
Family
ID=8122004
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP89111221A Expired - Lifetime EP0347845B1 (en) | 1988-06-20 | 1989-06-20 | Insulin precursors, their preparation, and dna sequences, expression vehicles and primers and a process for producing human insulin and analogues |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US5202415A (en) |
| EP (1) | EP0347845B1 (en) |
| JP (1) | JP2766999B2 (en) |
| KR (1) | KR0140238B1 (en) |
| AT (1) | ATE93239T1 (en) |
| AU (1) | AU618612B2 (en) |
| CA (1) | CA1337976C (en) |
| DE (1) | DE68908491T2 (en) |
| DK (1) | DK336188D0 (en) |
| ES (1) | ES2059627T3 (en) |
| FI (1) | FI102294B (en) |
| IE (1) | IE64303B1 (en) |
| NO (1) | NO177499C (en) |
| NZ (1) | NZ229615A (en) |
| PT (1) | PT90897B (en) |
| WO (1) | WO1989012647A1 (en) |
| ZA (1) | ZA894639B (en) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK105489D0 (en) * | 1989-03-03 | 1989-03-03 | Novo Nordisk As | POLYPEPTIDE |
| DK134189D0 (en) * | 1989-03-20 | 1989-03-20 | Nordisk Gentofte | INSULIN COMPOUNDS |
| DK72793D0 (en) * | 1993-06-21 | 1993-06-21 | Novo Nordisk As | NEW PRODUCT |
| US6001604A (en) * | 1993-12-29 | 1999-12-14 | Bio-Technology General Corp. | Refolding of proinsulins without addition of reducing agents |
| KR0150565B1 (en) * | 1995-02-15 | 1998-08-17 | 김정재 | A process for preparing human proinsulin by recombinant dna technology |
| GB9513967D0 (en) * | 1995-07-08 | 1995-09-06 | Univ Leicester | Insulin |
| KR100253916B1 (en) * | 1997-12-29 | 2000-05-01 | 김충환 | A process for preparing human proinsulin |
| US7169889B1 (en) | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
| US6777207B2 (en) | 1999-12-29 | 2004-08-17 | Novo Nordisk A/S | Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast |
| US7378390B2 (en) | 1999-12-29 | 2008-05-27 | Novo Nordisk A/S | Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast |
| US6521738B2 (en) | 1999-12-29 | 2003-02-18 | Novo Nordisk A/S | Method for making insulin precursors and insulin precursor analogs |
| WO2001049870A1 (en) | 1999-12-29 | 2001-07-12 | Novo Nordisk A/S | Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast |
| KR100449454B1 (en) * | 2000-10-02 | 2004-09-21 | 이현철 | Vector for Curing Diabetes Mellitus Containing Gene of Single-chain Insulin Analog |
| KR20030005204A (en) * | 2000-12-25 | 2003-01-17 | 가부시키가이샤 시세이도 | Sympathetic-activating perfume composition |
| US7060675B2 (en) * | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| US6867183B2 (en) * | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| WO2002079251A2 (en) * | 2001-04-02 | 2002-10-10 | Novo Nordisk A/S | Method for making human insulin precursors |
| US7105314B2 (en) | 2001-04-02 | 2006-09-12 | Novo Nordisk A/S | Method for making human insulin precursors |
| ATE443082T1 (en) * | 2001-04-02 | 2009-10-15 | Novo Nordisk As | INSULIN PRECURSORS AND METHOD FOR THE PRODUCTION THEREOF |
| US6858580B2 (en) * | 2001-06-04 | 2005-02-22 | Nobex Corporation | Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6713452B2 (en) * | 2001-06-04 | 2004-03-30 | Nobex Corporation | Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US7713932B2 (en) | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
| US6835802B2 (en) * | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
| US6828297B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6828305B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| AU2002316807A1 (en) * | 2001-06-08 | 2002-12-23 | Novo Nordisk A/S | Method for making insulin precursors and insulin precursor analogs |
| US20030040601A1 (en) * | 2001-06-08 | 2003-02-27 | Ivan Diers | Method for making insulin precursors and insulin analog precursors |
| US7196059B2 (en) * | 2001-09-07 | 2007-03-27 | Biocon Limited | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US7166571B2 (en) * | 2001-09-07 | 2007-01-23 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US7312192B2 (en) * | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US6913903B2 (en) * | 2001-09-07 | 2005-07-05 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US7601688B2 (en) * | 2002-06-13 | 2009-10-13 | Biocon Limited | Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus |
| WO2004085472A1 (en) * | 2003-03-27 | 2004-10-07 | Novo Nordisk A/S | Method for making human insulin precursors and human insulin |
| CN1836047B (en) | 2003-06-17 | 2010-12-22 | 赛姆生物系统遗传公司 | Methods for the production of insulin in plants |
| CA2580313C (en) * | 2004-07-19 | 2016-03-15 | Biocon Limited | Insulin-oligomer conjugates, formulations and uses thereof |
| KR101699370B1 (en) | 2006-09-22 | 2017-02-14 | 노보 노르디스크 에이/에스 | Protease resistant insulin analogues |
| CN101939023B (en) * | 2007-10-16 | 2016-08-03 | 百康有限公司 | Can peroral administration solid composite medicament and method thereof |
| WO2010149772A1 (en) | 2009-06-26 | 2010-12-29 | Novo Nordisk A/S | Preparation comprising insulin, nicotinamide and an amino acid |
| CN103249427A (en) | 2010-12-14 | 2013-08-14 | 诺沃—诺迪斯克有限公司 | Fast-acting insulin in combination with long-acting insulin |
| RU2013130374A (en) | 2010-12-14 | 2015-01-20 | Ново Нордиск А/С | THE PRODUCT CONTAINING INSULIN, NICOTINAMIDE AND AMINO ACID |
| WO2013186138A1 (en) | 2012-06-14 | 2013-12-19 | Novo Nordisk A/S | Preparation comprising insulin, nicotinamide and arginine |
| EP4086279A4 (en) | 2019-12-30 | 2024-08-07 | Gan & Lee Pharmaceuticals Co Ltd | Insulin derivative |
| AU2020418207A1 (en) | 2019-12-30 | 2022-08-25 | Gan & Lee Pharmaceuticals Co., Ltd. | Long-acting GLP-1 compound |
| CN118574842A (en) | 2022-01-28 | 2024-08-30 | 甘李药业股份有限公司 | Acylated insulin |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0037255B1 (en) * | 1980-03-27 | 1983-11-23 | Eli Lilly And Company | Process for producing an insulin precursor |
| EP0163529A1 (en) * | 1984-05-30 | 1985-12-04 | Novo Nordisk A/S | Insulin precursors, process for their preparation and process for preparing human insulin from such insulin precursors |
| EP0195691A1 (en) * | 1985-03-22 | 1986-09-24 | Novo Nordisk A/S | Process for the preparation of Insulin Precursors and process for the preparation of human insulin |
| EP0254516A2 (en) * | 1986-07-21 | 1988-01-27 | Novo Nordisk A/S | Novel Peptides |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4430266A (en) * | 1980-11-28 | 1984-02-07 | Eli Lilly And Company | Process for producing an insulin precursor |
| US5015575A (en) * | 1983-04-07 | 1991-05-14 | Chiron Corporation | Hybrid DNA synthesis of insulin |
| DE3327928A1 (en) * | 1983-08-03 | 1985-02-21 | Hoechst Ag, 6230 Frankfurt | METHOD FOR PRODUCING INSULIN DERIVATIVES |
| US4946828A (en) * | 1985-03-12 | 1990-08-07 | Novo Nordisk A/S | Novel insulin peptides |
| DK437786D0 (en) * | 1986-09-12 | 1986-09-12 | Nordisk Gentofte | insulin precursors |
| KR900701842A (en) * | 1988-07-20 | 1990-12-04 | 헨리 브뢰늄 | Human insulin homologues and formulations comprising them |
| KR910700262A (en) * | 1988-12-23 | 1991-03-14 | 안네 제케르 | Human insulin analogues |
-
1988
- 1988-06-20 DK DK336188A patent/DK336188D0/en not_active Application Discontinuation
-
1989
- 1989-06-19 JP JP1507202A patent/JP2766999B2/en not_active Expired - Fee Related
- 1989-06-19 US US07/623,739 patent/US5202415A/en not_active Expired - Lifetime
- 1989-06-19 AU AU38600/89A patent/AU618612B2/en not_active Ceased
- 1989-06-19 ZA ZA894639A patent/ZA894639B/en unknown
- 1989-06-19 PT PT90897A patent/PT90897B/en not_active IP Right Cessation
- 1989-06-19 IE IE197689A patent/IE64303B1/en not_active IP Right Cessation
- 1989-06-19 WO PCT/DK1989/000152 patent/WO1989012647A1/en active IP Right Grant
- 1989-06-19 CA CA000603208A patent/CA1337976C/en not_active Expired - Fee Related
- 1989-06-20 ES ES89111221T patent/ES2059627T3/en not_active Expired - Lifetime
- 1989-06-20 DE DE89111221T patent/DE68908491T2/en not_active Expired - Lifetime
- 1989-06-20 AT AT89111221T patent/ATE93239T1/en not_active IP Right Cessation
- 1989-06-20 EP EP89111221A patent/EP0347845B1/en not_active Expired - Lifetime
- 1989-06-20 NZ NZ229615A patent/NZ229615A/en unknown
-
1990
- 1990-02-20 KR KR90700348A patent/KR0140238B1/en not_active IP Right Cessation
- 1990-12-19 FI FI906285A patent/FI102294B/en not_active IP Right Cessation
- 1990-12-19 NO NO905470A patent/NO177499C/en unknown
-
1992
- 1992-09-23 US US07/952,696 patent/US5324641A/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0037255B1 (en) * | 1980-03-27 | 1983-11-23 | Eli Lilly And Company | Process for producing an insulin precursor |
| EP0163529A1 (en) * | 1984-05-30 | 1985-12-04 | Novo Nordisk A/S | Insulin precursors, process for their preparation and process for preparing human insulin from such insulin precursors |
| EP0195691A1 (en) * | 1985-03-22 | 1986-09-24 | Novo Nordisk A/S | Process for the preparation of Insulin Precursors and process for the preparation of human insulin |
| EP0254516A2 (en) * | 1986-07-21 | 1988-01-27 | Novo Nordisk A/S | Novel Peptides |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2059627T3 (en) | 1994-11-16 |
| AU3860089A (en) | 1990-01-12 |
| FI102294B1 (en) | 1998-11-13 |
| EP0347845A2 (en) | 1989-12-27 |
| FI102294B (en) | 1998-11-13 |
| KR900701841A (en) | 1990-12-04 |
| US5202415A (en) | 1993-04-13 |
| PT90897A (en) | 1989-12-29 |
| PT90897B (en) | 1995-03-31 |
| ZA894639B (en) | 1991-12-24 |
| CA1337976C (en) | 1996-01-23 |
| EP0347845B1 (en) | 1993-08-18 |
| FI906285A0 (en) | 1990-12-19 |
| DK336188D0 (en) | 1988-06-20 |
| KR0140238B1 (en) | 1998-07-01 |
| DE68908491D1 (en) | 1993-09-23 |
| ATE93239T1 (en) | 1993-09-15 |
| NO905470L (en) | 1991-02-18 |
| NZ229615A (en) | 1991-03-26 |
| NO905470D0 (en) | 1990-12-19 |
| IE891976L (en) | 1989-12-20 |
| NO177499B (en) | 1995-06-19 |
| NO177499C (en) | 1995-09-27 |
| WO1989012647A1 (en) | 1989-12-28 |
| IE64303B1 (en) | 1995-07-26 |
| JP2766999B2 (en) | 1998-06-18 |
| JPH03505206A (en) | 1991-11-14 |
| AU618612B2 (en) | 1992-01-02 |
| US5324641A (en) | 1994-06-28 |
| DE68908491T2 (en) | 1994-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0347845A3 (en) | Insulin precursors, their preparation, and dna sequences, expression vehicles and primers and a process for producing human insulin and analogues | |
| NO174351C (en) | Process for producing human insulin precursor, as well as DNA sequence and vector for use of the method | |
| SG49097A1 (en) | Nucleotide sequences coding for a protein with urease activity | |
| ES2009238A6 (en) | Mycobacterial recombinants and peptides | |
| CA2263889A1 (en) | P-selectin ligand proteins | |
| EP0305488A4 (en) | Mycobacterial recombinants and peptides | |
| CA2155185A1 (en) | Totally synthetic affinity reagents | |
| BG102973A (en) | LIGAND RET (RetL) FOR THE STIMULATION OF THE NERVE AND RENAL GROWTH | |
| CA2385857A1 (en) | C peptide for improved preparation of insulin and insulin analogs | |
| CA2392840A1 (en) | Method for making insulin precursors and insulin precursor analogs | |
| AU7565991A (en) | Variant cd44 surface proteins, dna sequences coding them, antibodies against these proteins and their use in diagnosis and therapy | |
| CA2147623A1 (en) | Novel p-selectin ligand protein | |
| CA2179909A1 (en) | Ligand that binds fas antigen | |
| EP0374044A3 (en) | Tgf - beta 1 / beta 2 : a novel chimeric transforming growth factor-beta. | |
| WO1995030001A3 (en) | Novel p-selectin ligand protein | |
| CA2209298A1 (en) | Mpl ligand analogs | |
| ES2007110A6 (en) | Insulin precursors. | |
| EP0832109A4 (en) | Fibroblast growth factor homologous factor-2 and methods of use | |
| DK301090A (en) | insulin precursors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
| 17P | Request for examination filed |
Effective date: 19901211 |
|
| PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
| RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: NOVO NORDISK A/S |
|
| AK | Designated contracting states |
Kind code of ref document: A3 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
| RHK1 | Main classification (correction) |
Ipc: C07K 15/00 |
|
| 17Q | First examination report despatched |
Effective date: 19921016 |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
| REF | Corresponds to: |
Ref document number: 93239 Country of ref document: AT Date of ref document: 19930915 Kind code of ref document: T |
|
| REF | Corresponds to: |
Ref document number: 68908491 Country of ref document: DE Date of ref document: 19930923 |
|
| ITF | It: translation for a ep patent filed | ||
| ET | Fr: translation filed | ||
| REG | Reference to a national code |
Ref country code: GR Ref legal event code: FG4A Free format text: 3009802 |
|
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
| EPTA | Lu: last paid annual fee | ||
| 26N | No opposition filed | ||
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2059627 Country of ref document: ES Kind code of ref document: T3 |
|
| EAL | Se: european patent in force in sweden |
Ref document number: 89111221.1 |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: IF02 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 20020612 Year of fee payment: 14 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: ES Payment date: 20020618 Year of fee payment: 14 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GR Payment date: 20020626 Year of fee payment: 14 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 20020628 Year of fee payment: 14 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 20020708 Year of fee payment: 14 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 20020821 Year of fee payment: 14 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20030620 Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20030620 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20030621 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20030630 |
|
| BERE | Be: lapsed |
Owner name: *NOVO NORDISK A/S Effective date: 20030630 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20040101 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20040107 |
|
| NLV4 | Nl: lapsed or anulled due to non-payment of the annual fee |
Effective date: 20040101 |
|
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20030621 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20050620 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 20080609 Year of fee payment: 20 Ref country code: CH Payment date: 20080710 Year of fee payment: 20 Ref country code: DE Payment date: 20080626 Year of fee payment: 20 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20080617 Year of fee payment: 20 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20080625 Year of fee payment: 20 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: PE20 Expiry date: 20090619 |
|
| EUG | Se: european patent has lapsed | ||
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GB Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20090619 |